Project Summary The present application is in response to Strategies 1.3 and 2.2 of the NIMH strategic plan, which respectively call for the identification of brain circuits that contribute to various aspects of mental function and dysfunction and the identification of clinically useful biomarkers and behavioral indicators that predict change across illness trajectories. We propose to contribute to these goals by applying the Research Domain Criteria (RDoC) approach to the symptom of paranoia and attempting to identify a neurobehavioral mechanism for paranoid ideation. Paranoia is a distressing and debilitating psychotic symptom that is both transdiagnositic and dimensional in that it is experienced by individuals across a wide range of psychiatric diagnoses and is commonly experienced by individuals in the general population. The current proposal conceptualizes paranoia as lying at the intersection of two Domains: Social Processes (specifically, Perception and Understanding of Others and Reception of Facial Communication) and Negative Valence Systems (specifically, Sustained Threat). Existing knowledge links each of these constructs to function of the amygdala, and our pilot work demonstrates that paranoia is associated with increased baseline activity of amygdala and related neural circuits. We therefore hypothesize that increased tonic, or baseline, activity of social process and negative valence neural circuits will constitute a neurobehavioral mechanism for paranoia across the continuum from healthy to pathological. To test this hypothesis, data will be collected across three RDoC Units of analysis ? circuits (baseline and stimulus-related neural activity), behavior (judgments of trustworthiness and emotion from facial stimuli), and self-report (paranoia and social functioning rating scales). These data will be used to test longitudinal associations between our proposed mechanism and paranoid ideation (Aim 1), determine if experimentally induced paranoia yields predicted changes in the proposed mechanism (Aim 2), and establish how our proposed neurobehavioral mechanism varies dimensionally across the paranoia continuum (Aim 3). The findings of this project will not only contribute to new classification strategies that utilize neurobiological measures but also to the identification of novel treatment targets and biologically-based predictors of illness trajectory.